- 9/6/2024
Penicillin binding protein (PBP) receptor
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00:00Let's continue our discussion about antibiotics. This is Medicosis Perfectionalis, where medicine makes perfect sense. Today, we'll talk about
00:07penicillins.
00:09Penicillins cover gram-positive cocci, gram-positive rods, gram-negative cocci, and
00:16spirochetes, such as syphilis, caused by the nasty trypanema pallidum.
00:20The cell wall synthesis inhibitors include the beta-lactams, which include penicillins,
00:24syphilosporins,
00:27carbapenem, and monobactam, such as the famous
00:29Estreonam.
00:31Repetition is the mother of pedagogy. Here are antibiotics, antibacterials, the cell wall, such as beta-lactams,
00:38which include penicillin, syphilosporin,
00:41carbapenem, and monobactam, such as the one and only Estreonam. Penicillins are four groups.
00:48Natural penicillins,
00:50anti-staphylococcal penicillins,
00:52amino penicillins, or
00:55anti-pseudomonopenicillins. All of them are sensitive to the beta-lactamase, also known as penicillinase,
01:03except the
01:05anti-staphylococcal penicillins. So let's talk about the natural penicillins. Penicillin G, which is an injection,
01:11penicillin V is an oral medication.
01:14The anti-staph include the obsolete methicillin, and then oxcloxdecloxenaf for staph,
01:21especially if it's sensitive to methicillin.
01:24Amino penicillin are the ampicillin and amoxicillin. They can cause a rash in patients with
01:30infectious mononucleosis,
01:33those teenagers with the kissing disease due to Epstein-Barr virus, and the atypical
01:39CD8 positive T lymphocyte. And then the anti-pseudomonopenicillins are carbenicillin,
01:45ticercillin, papiricillin, azlocillin. And then the cephalosporins, and they will include five generations.
01:52First generation is more gram-positive, second generation is more gram-positive, third generation is more gram-negative, fourth generation more gram-negative,
02:00fifth generation is gram-positive and gram-negative, such as the famous
02:06ceftaroline. It covers MRSA, but it does not cover pseudomonas.
02:11Here is the world before penicillin. We had the black death, also known as the plague,
02:15we had cholera with vomiting and watery diarrhea, and we had puerperal sepsis.
02:21Then came this nice Scottish gentleman who lives in England, Dr. Alexander Fleming, or
02:29Sir Alexander Fleming. He discovered penicillin.
02:34Penicillin, look at the name, penicillin. What does IN mean? It means it's a protein.
02:39Penicillin, yes, because it's
02:42extracted from the fungus
02:45Penicillium notatum. Here is the same case from the last lecture.
02:50What's the best treatment option for this patient? Please pause.
02:56And the answer is, since this is primary syphilis,
03:00this is the chancre, the answer will be G. One dose of intramuscular
03:06benzathine penicillin, or penicillin G, 2.4 million units. You forget your name,
03:12but you don't forget the penicillin G. Let's talk about
03:16penicillins, which are part of the beta-lactam
03:20antibiotics. Why do we call them beta-lactams? Because they inhibit the beta-lactams,
03:25which are part of the cell wall in the freaking bacteria. Human beings do not have a cell wall,
03:31but bacteria do, and when they do, it has beta-lactam.
03:36Penicillins are divided into four groups. Number one are the natural penicillins.
03:40These are beta-lactamase sensitive, which means they can be destroyed by the bacterial
03:46penicillinase, also known as beta-lactamase. The second group is beta-lactamase
03:52resistant penicillin, such as the obsolete methicillin and oxcloxdecloxan F.
03:57The third group is the amino penicillin, such as ampicillin and amoxicillin.
04:03Those are sensitive to beta-lactamase. In fact, all of them are sensitive to beta-lactamase, except those
04:10anti-staphylococcal penicillins. Next, we have the beta-lactamase sensitive
04:16anti-pseudomonal penicillin, such as papiracin, ticercilin, carbenicillin, azalocilin, etc.
04:21If you are beta-lactamase sensitive, such as the first group, the third group, and the fourth group,
04:27you should add a beta-lactamase inhibitor
04:31together with the penicillin, such as clavulanic acid or clavulanate,
04:35solbactam or tezobactam. Please remember the famous
04:40anti-pseudomonal therapy
04:42papiracilin-tezobactam, also known as PIPTEZO in short.
04:48Four groups of penicillins, natural penicillins, penicillin G and penicillin V,
04:53anti-staph, oxcloxdecloxan F, F for staph,
04:57amino penicillins, ampicillin and amoxicillin. Anti-pseudomonals are carbenicillin, ticercilin, papiracilin, azalocilin.
05:04All of them are sensitive to beta-lactamase except the anti-staphylococcal.
05:10If you are sensitive to beta-lactamase, we should add a beta-lactamase
05:14inhibitor with you, such as
05:17clavulanic acid, solbactam, tezobactam. Let's talk about penicillins. They are cell wall synthesis inhibitors.
05:23They are beta-lactam inhibitors or beta-lactam antibiotics. They are bactericidal.
05:28They destroy the fricking bacteria because they inhibit the synthesis of the cell wall. How do they work?
05:34They bind something called penicillin-binding protein on the bacteria. They inhibit something called
05:40transpeptidase or transpeptidation, which is probably the last step in the synthesis of the cell wall of the fricking
05:48bacteria, i.e. they inhibit cross-linking of the bacterial cell wall.
05:53Here is the nice penicillin and this square is known as the beta-lactam ring.
06:00The ugly bacterial beta-lactamase destroys this beta-lactam ring,
06:06rendering the penicillin ineffective.
06:08That's why if you are sensitive to beta-lactamase, we should add a beta-lactamase
06:14inhibitor with you, such as solbactam, tezobactam, clavulonate.
06:19This beta-lactam ring will determine the stability of the drug as well as the spectrum of activity of the antibiotics.
06:27They are excreted in the kidney. All of the penicillins except ox, clox, diclox, and nef.
06:34Ox, clox, diclox, and nef are always the exceptions. All penicillins are sensitive to beta-lactamase
06:40except ox, clox, diclox, and nef. All penicillins are excreted renally except ox, clox, diclox, and nef.
06:47They are excreted through the bile.
06:50Penicillin cannot pass through the blood-brain barrier and cannot enter the CNS
06:57except if your meninges are inflamed. So in meningitis, penicillin can actually help.
07:04Penicillin can be given orally,
07:07intravenously, or intramuscularly.
07:10Penicillin V is oral.
07:12Penicillin G is injectable.
07:15Here is the last step in cell wall synthesis of the cell wall of the bacteria. You get peptidoglycan and peptidoglycan.
07:22These are two polymers. You add them together. You cross-link them together.
07:27You cleave the D-ala-D-ala and you form a new peptide bond. This is called pentaglycine chain.
07:34This is called transglycosylation or elongation. And then you form the bacterial cell wall.
07:42All right, how does penicillin work? Penicillin inhibits the transpeptidase by binding to something called the penicillin
07:50binding protein. Then vancomycin is another drug, works by another cross-linking enzyme.
07:56It inhibits that enzyme and
07:59vancomycin is only for gram-positive while penicillin can be for gram-positive and
08:04negative. Both penicillin and vancomycin are bactericidal.
08:09Penicillin can also work by activating
08:12otolytic enzyme, punching holes in the cell wall of the bacteria, destroying the bacteria. That's why it's a bactericidal.
08:20Syphilis. The first treatment for syphilis was mercury.
08:23Yes, using an actual toxin to treat syphilis because this is the only thing we had.
08:30The next thing that we tried was called arsphenamine or
08:35salvarsan
08:36Invented or discovered by the great German physician Paul Ehrlich. Then we had neoarsphenamine or
08:44neo-salvarsan and then today we use penicillin to treat syphilis
08:50specifically penicillin G, which is a freaking injection.
08:54Here's a nice needle.
08:57Penicillins. They have the beta-lactam ring. We divide penicillins into two groups.
09:01Beta-lactam is sensitive. All of them except ox, cloxyl, lax, and neb,
09:07these are beta-lactamase resistant. If you are sensitive to beta-lactamase,
09:11you should add a beta-lactamase inhibitor to that, such as
09:17clavirinic acid, solubactam, tezobactam.
09:20Penicillins. If the penicillin is sensitive to beta-lactamase,
09:23you should add a beta-lactamase inhibitor such as avibactam, solubactam, tezobactam, and clavirinic acid.
09:29These are called suicide inhibitors to inhibit or cause suicide to the beta-lactamase, which is made by the bacteria to
09:37resist the penicillin.
09:39We have certain combinations that are famous. Amoxicillin, clavirinate,
09:44please do not ever forget that, and this is used for cat bites, dog bites, human bites,
09:51all of these bites. By the way, human bites are worse than cat bites or dog bites.
09:57Human bites are the worst.
10:00Ampicillin, solubactam,
10:02Pepericillin, tezobactam, which is also known as pep-tezo, and
10:07Ticercillin, clavirinate. Ox, Clox, Zyclox, and F are resistant, do not combine them with anything.
10:13Side effects of penicillins in general include GI upset,
10:17this is the most common side effect, zoonasia, vomiting, diarrhea, disruption of the normal flora, or a super infection. Next,
10:23we have hypersensitivity reaction, usually type 1 or immediate type hypersensitivity reaction,
10:28you know, the mast cells, and the basophils, and the IgE, and the eosinophils, and the histamine, and it can range from
10:35maculopapular rash, just some spots on your skin, all the way to
10:41anaphylaxis, which is life-threatening, and in between you could have exfoliative dermatitis,
10:47bronchospasm, or angioedema. This is a huge spectrum.
10:51Why do we have hypersensitivity against penicillin? It's due to a heptin. We form
10:58antibodies against this heptin. What do you mean by heptin? It's a baby antigen.
11:02What kind of heptin is that? It's the penicilloic acid,
11:06which is inside of the penicillin, when it links to a lysine residue on the protein, forms something that's
11:13immunogenic, and it's gonna be attacked by your antibodies, and this is a hypersensitivity reaction, type 1 or
11:20immediate type to be specific, happens within seconds or within minutes. There is cross
11:27allergenicity among individual penicillin. In other words, if you are allergic to penicillin G,
11:34you will also be allergic to the
11:37ampicillin, amoxicillin,
11:39ticurcillin, etc. They are in the same family. After all, they are penicillins.
11:45Penicillins can lead to
11:47pseudomembranous colitis,
11:49especially ampicillin. So far, you should know about four
11:54antibiotics that can cause pseudomembranous colitis. Number one,
11:58ampicillin. Number two,
12:01clindamycin. Number three,
12:03carbapenem. Number four,
12:05monobactam, such as the one and only astreonam.
12:09Penicillins can cause rashes if you have infectious
12:13mononucleosis, the kissing disease. Kissing plus aminopenicillin plus a virus, usually
12:18Epstein-Barr virus, equals a rash. What kind of rash is it? It's a maculopapular rash.
12:24They are flat lesions with tiny elevations.
12:29Methicillin can lead to interstitial nephritis. That's why methicillin is now obsolete.
12:34Acute hepatitis. Your liver is on fire.
12:37Platelet dysfunction. Penicillins can inhibit platelet aggregation. Do not give penicillin with
12:44warfarin, because
12:46penicillin will inhibit your primary
12:49hemostasis, warfarin will inhibit your secondary hemostasis, and you will bleed to death.
12:55High doses of penicillin, like any penicillin, can lead to seizure,
13:01especially in patients with epilepsy,
13:04especially with
13:05intrathecal injection. Remember that penicillin cannot go into the brain.
13:10Sometimes we give it intrathecally. This can increase your risk of seizure. Last one is the Gerrish-Herxheimer reaction.
13:17Happens within 24 hours after injecting penicillin. This is an acute
13:23febrile reaction. Happens when treating syphilis, due to rupture of all of the trypanema
13:29pallidums, and this is
13:32like
13:34immunogenic. You will form antibodies against those trypanema particles, and
13:39this is the acute febrile reaction known as Gerrish-Herxheimer reaction.
13:44Penicillins are excreted by the kidney, except oxaloxacloxanab, they are excreted in the bile.
13:50Let's talk about renal excretion. It's
13:54inhibited by probanocid. Therefore, probanocid will prolong the half-life of the penicillin,
14:00promoting penicillin toxicity. Here is
14:03hypoxanthine and xanthine. This is the xanthine.
14:06This is, of course, the uric acid salvage pathway or purine salvage pathway.
14:12This is xanthine oxidase.
14:14This is also xanthine oxidase. Giving us uric acid, uric acid will end up in the toilet. How to
14:20prevent the formation of uric acid or actually cure gout or mitigate the symptoms of gout?
14:27You have allopurinol, which inhibits the xanthine oxidase. Feboxostat, which actually STAT means inhibit, and
14:34XO is the xanthine oxidase. Now, you do not have xanthine,
14:38you do not have uric acid. Or, if you already have uric acid, we can
14:44stimulate this
14:46respiricase by probanocid, and this will stimulate the excretion of the uric acid in the urine, and
14:53uric acid will end up in the toilet, go to hell.
14:56But, giving aspirin can actually inhibit the respiricase, which can theoretically
15:02worsen the gout, although it depends on the dose. So, probanocid
15:07stimulates the secretion of uric acid, but inhibits the secretion of penicillins,
15:13cephalosporins, and amipenem, which is a carbapenem.
15:16Therefore, probanocid is good if you have gout, and it's good if you are taking beta-lactams, because it
15:23potentiates the beta-lactams. But, of course, too much will potentiate the toxicity of the beta-lactam antibiotics.
15:30Penicillins except, these are my notes, all of them, all penicillins are renally excreted except
15:37OX, CLOX, ZYCLOX, and NEF. All of the penicillins cannot enter the CNS except when your meninges are inflamed.
15:44All of the penicillins are beta-lactamase sensitive except, same for OX, CLOX, ZYCLOX, and NEF,
15:50these are beta-lactamase resistant, there is no need to give a beta-lactamase inhibitor. All of the penicillins can reach most
15:58tissue except the cirrhosal cavity, the three Ps, pleura,
16:02peritoneum, and pericardium.
16:04Again, penicillins are either beta-lactamase sensitive, all of them except OX, CLOX, ZYCLOX, and NEF,
16:10these are beta-lactamase resistant. Four classes of penicillins, natural penicillin, G and V, anti-staphylococcal,
16:17OX, CLOX, ZYCLOX, and NEF, amino, ampi, and amoxy,
16:21antipsydumonal, carbenicillin, ticaricillin, papiricillin, azlucillin, all of them are beta-lactamase sensitive except number two,
16:28therefore you should combine them with a beta-lactamase inhibitor.
16:32Let's talk about each class. First, the natural penicillins, G and V. V is oral, here is oral,
16:39your mouth, like a V, and penicillin G is injectable, G, it hurts,
16:45does not penetrate the CNS unless the meninges are inflamed,
16:48we already know that, we use penicillin G for syphilis, you are allowed to forget your name, but do not forget that
16:56penicillin G treats syphilis, there out is injection, intramuscular intravenous, penicillin V is oral,
17:02it's used for group A, beta-hemolytic streptococci, or GAPs, and it's oral.
17:09Penicillin G and penicillin V are penicillinase sensitive, therefore you should combine them with a penicillinase inhibitor.
17:16The next group of penicillins are the anti-staphylococcal penicillins, these are resistant to beta-lactamase,
17:22there is no need to combine them with the beta-lactamase inhibitors,
17:25they include methicillin, which is no longer used because it caused interstitial nephritis,
17:30what's used now is ox, clox, diclox, and nef, these are excreted to the bile, use nef for
17:37staph. In the beginning, staph aureus was sensitive to methicillin,
17:41I mean ox, clox, diclox, and nef, then the staph aureus became resistant to methicillin,
17:47I mean ox, clox, diclox, and nef, we called it MRSA, and then we developed a new drug,
17:52vancomycin, to actually treat the MRSA, then the MRSA, it became smarter, and it's now resistant to vancomycin called Versa,
17:59so we developed a new drug called lenisolid to deal with the Versa,
18:04also daptomycin is the same thing, Versa, lenisolid is good for Versa,
18:10which is vancomycin-resistant staph aureus, as well as VRA, vancomycin-resistant enterococci.
18:18The third class is the aminopenicillins, the ampicillin and amoxicillin, these are
18:23beta-lactamase sensitive, therefore you should combine them with a beta-lactamase inhibitor,
18:27they cover H. influenzae, E. coli, listeria, big time, listeria is treated with penicillin,
18:33protease, salmonella, and shigella, salmonella causes food poisoning, shigella causes hemorrhagic
18:39diarrhea, or bloody diarrhea, all of these suckers are gram negative, enterococci are gram positive,
18:47aminopenicillins cover both of them, ampicillin is here, amoxicillin is here, we can combine the
18:53aminopenicillins with aminoglycosides to achieve synergy, which means one plus one equals three,
19:00this decreases resistance and it's very good to treat endocarditis, you treat endocarditis by
19:05combining an aminopenicillin with an aminoglycoside, two aminos together, amen, also combine them with
19:13beta-lactamase inhibitors such as solbactam, tasobactam, clavrinate to increase spectrum
19:18and efficacy, ampicillin is IV for the gram negatives, amoxicillin is oral, either one can
19:25lead to rash in cases of infectious mononucleosis, actually if you have infectious mononucleosis
19:32and your doctor gave you an aminopenicillin, you have almost a 100% chance of getting rash,
19:42amoxicillin can be used for otitis media and community acquired pneumonia, both of them of
19:47course can lead to hypersensitivity reaction because they are penicillins after all,
19:52next we have the amoxicillin which is an aminopenicillin, we use it for treatment of
20:00otitis media, sinusitis, it causes rash in kissing disease and in mononucleosis you have tonsillitis
20:09as well as palatal petechiae, also in infectious mononucleosis you have maculopapular rash and
20:17generalized lymphadenopathy, here is a nice lymph node, okay so here is my mnemonic for the kissing
20:23disease mononucleosis, hey babe let's kiss some maculopapular rash, let's take some aminopenicillin
20:31to cause a rash, we have a 100% probability of making it, wink wink, i'll see you tonight,
20:40back to amoxicillin, we use it for otitis, sinusitis, community acquired pneumonia,
20:47but the bad news is it can cause pseudomembranous colitis by the nasty C difficile,
20:55also we can use amoxicillin to treat gi and gu infections, if this is called the kissing disease
21:03remember that amoxicillin is an oral medication because your mouth is used for kissing actually,
21:10it's the only organ that you can kiss with, the fourth class of penicillins are the anti-pseudomonal
21:16penicillins, they are beta-lactamase sensitive therefore you should combine them, we divide them
21:20into two groups, the first group is carpenicillin and ticercillin, the next one is pepericillin and
21:25azlocillin, remember the pep-tazo, very very famous, pepericillin-tazo-bactam, we use it for
21:32severe nosocomial infection, they are called anti-pseudomonal penicillins therefore we use
21:37them against pseudomonas, imagine my shock, and other gram-negative rods because as you know
21:42pseudomonas is a gram-negative rod, side effect hypersensitive reaction as always, you can combine
21:49them with aminoglycosides to achieve synergy, which means one plus one equals three, penicillins cover
21:56the gram-positive cocci, gram-positive rods, gram-negative cocci such as nosuria meningitis
22:04because penicillin cannot enter your CNS unless your meninges are inflamed, unless you have
22:11meningitis, also penicillin can treat syphilis, you may forget your name but please do not forget
22:17that penicillin G treats syphilis. Is penicillin G an oral medication or an injectable medication?
22:24It's an injection. G, it hurts. Here is a table just for the penicillins, here are the natural
22:32penicillins, here are the anti-staph, amino penicillins, and anti-pseudomonas, the natural
22:38penicillins they cover gram-positive cocci such as the group A beta hemolytic strep,
22:42the nosuria meningitis, and the trypanema palatum for syphilis, the anti-staph are just for staph,
22:49and staph is a gram-positive cocci, amino penicillins for enterococci, listeria which
22:54is a gram-positive rod, and then for the gram-negative cocci such as H influenza which
23:02is actually a gram-negative cocco bacilli, and salmonella and E. coli, these are gram-negative
23:09rods, the anti-pseudomonas of course are for pseudomonas, and here is everything that you
23:14need to know about penicillins in just one slide. Please take about two minutes to read it and
23:22understand everything in it because this is just pure gold. Side effects of penicillin, remember
23:28the type 1 hypersensitivity reaction which is a huge spectrum ranging from just a maculopapular
23:35rash all the way up to an anaphylaxis with an exfoliative dermatitis, bronchospasm, angioedema
23:43in between. This is a type 1 hypersensitivity rash and hypotension. Hypotension is the prophylaxis,
23:49bronchospasm, wheezing, etc. This is IgE, this is the mast cell, this is the histamine, this is the
23:56eosinophil later on. Also penicillin can lead to type 2 hypersensitive reaction with hemolysis
24:02and jaundice. It can lead to a serum sickness-like reaction as well, but the most common one is a type
24:091 hypersensitivity reaction. Please don't ever forget that. Here are aspirin drug-drug interactions.
24:17Do not give aspirin with warfarin. Aspirin destroys your primary hemostasis, warfarin destroys your
24:25secondary hemostasis. Also do not give aspirin with penicillin G for the same reason.
24:32Aspirin is anti-platelet. Penicillin G decreases the number of platelets. Both are bad for your
24:37platelets. You have increased risk of penicillin toxicity and bleeding. Also do not combine penicillin
24:44G with warfarin. This damages your primary hemostasis, warfarin damages your secondary
24:50hemostasis, and you will increase your risk of bleeding. Quick review of syphilis. It's an STI,
24:57highly curable with penicillin. It's caused by the tryponema pallida. How do we treat syphilis?
25:03Single dose of penicillin G intramuscularly, 2.4 million units. This is primary syphilis.
25:09Secondary syphilis is another dose, but it's still penicillin G. If the patient is allergic
25:14to penicillin, give doxycycline twice a day for 14 days. But if it's penicillin, just a single
25:21shot, which is amazing. Transmission. First we have the primary syphilis, which is an STI,
25:26and then the secondary, and then the tertiary. This is just one way of getting it. Also you can
25:31get the congenital syphilis through vertical transmission from mommy to the baby during labor.
25:38The primary syphilis is a painless chancre on the penis. It's a single chancre, which is painless.
25:45This is diagnosed by the dark field microscopy. Culturing the lesion on the penis is freaking
25:52impossible. Forget it. Then the secondary syphilis is a rash. Between the primary and secondary,
25:58the chancre disappears. Just give it three to six weeks, and you will end up with the
26:02secondary syphilis. This is the rash. This is the condyloma latum. The rash is maculopapular,
26:10and it involves the trunk, the extremities, and the palms and the soles. The palms of the head
26:17and the soles of the feet. And then the rash will disappear. Give it two years, and you will have
26:23tertiary syphilis, the neurosyphilis, the tabes dorsalis, and maybe 10 to 15 years later after
26:31the secondary, you will have aortitis, which is specifically an ascending aortitis, which can lead
26:38to aortic regurgitation on auscultation. Syphilis primary, secondary, latent between secondary and
26:46tertiary, and then tertiary primary. Painless chancre and painless bilateral lymphadenopathy
26:51diagnosis, dark field microscopy. Do not use serology because it will give you a high false
26:57negative rate. Culture is impossible for get treatment. Single dose of penicillin G intramuscularly.
27:03Patient is allergic. Give doxy or azithromycin. Then it will disappear, and then you will come
27:09to the secondary syphilis. Disseminated skin lesion, maculopapular rash on the trunk, extremities,
27:13palms, and soles. Condyloma lata is anogenital, fever, and generalized lymphadenopathy diagnosis.
27:19We have two screen tests and two confirmatory tests. These are highly sensitive. These are
27:24highly specific. The screen tests include the rapid plasma reagent and the VDRL. The confirmatory
27:30include FTA, ABS, and the MHATPA or TP or whatever. So what's the treatment here? Three doses, not just
27:38one, but three doses of intramuscular penicillin G each given weekly. So the first dose, and then
27:46you wait one week. The second dose, you wait one week, and the third dose. The patient is allergic,
27:51doxy, or azithromycin. So secondary syphilis. Here is my mnemonic. The rule of twos. Everything here
27:59is two. Okay, secondary syphilis. Rash and condyloma lata. Fever and generalized lymphadenopathy.
28:07Screening and confirmatory. The screening, RPR, and VDRL. These are two. Confirmatory, FTA, ABS,
28:17MHATPA. Everything is two except the doses are three. After the secondary syphilis goes away,
28:25you get the latent syphilis. We have early and late phases of latent syphilis. Early happens
28:32within one year of the resolution of the secondary syphilis. Late happens more than one year after
28:38the resolution of syphilis. Early latent is treated the same way as the secondary syphilis
28:44with three doses of intramuscular penicillin G if the patient is allergic, give doxycycline.
28:50Third, tertiary syphilis, the gamma, the caseating granuloma. By the way, syphilis can have something
28:57called the gamma, which is a caseating granuloma, or a diffuse syphilitic reaction, which is a
29:04non-caseating granuloma. Both of them can happen in a patient with tertiary syphilis. Ascending
29:11aortitis, the vase of azorem, the tree bark appearance, and the aortic regurgitation,
29:16neurosyphilis, anterior uveitis, tabus dorsalis, which affects the dorsal root ganglia and the
29:21dorsal column of the spinal cord, causing ataxia and decreased proprioception with positive Romberg
29:26test and Argyle-Robertson pupil. This pupil can accommodate but cannot react to light.
29:34Here are the tests that are used to diagnose syphilis. I will leave you to read them.
29:39Just remember that VDRL and RPR may be positive in lupus. Whoa, like I'm trying to diagnose syphilis
29:48and they are positive and the patient does not have syphilis, but had lupus? Yes, indeed, because
29:53they interact with something called cardiolipin. Let's talk about spirochetes. There are three
30:00main spirochetes, tryponema, borrelia, and leptospira. Tryponema causes a disease called
30:06syphilis. Borrelia causes a disease called Lyme's disease. Leptospira causes leptospirosis.
30:12Tertiary syphilis and Lyme disease, both of them can cause anterior uveitis. The spirochetes can
30:19be diagnosed by dark field microscopy. You see the motile spirochetes under the microscope.
30:25Now, let's talk about Paul Ehrlich. We have two Paul Ehrlichs in history. The first one is a
30:31doofus. The second one is a great scientist who invented salversan, among others. Let's start with
30:39the doofus. Paul Ehrlich. He said this. He wrote a famous book called The Population Bomb. He said
30:46there will be worldwide famines in the 1970s and the 1980s due to overpopulation, which never
30:54happened. What happened is obesity and diabetes. He also said this. I would take even money that
31:01England will not exist in the 2000s. We are in 2019 or 2020 and England is still there. He also
31:10predicted that the death rates will go up due to overpopulation, but between this year and today,
31:17overall the death rates are going down, not up. And he also said this garbage statement,
31:24this horrible evil thing that I will not even utter. And then came a very smart guy called
31:30Julian Simon, an economist and a business professor. He said, look Paul, here are your
31:36bets. Here is a wager. Okay. If you win this, you'll get $10,000. If I win, I get $10,000.
31:43Okay. What's the deal? You pick five raw materials and I can guarantee you their cost will decline
31:50in the next 10 years. Look at the audacity of the economist. He let Paul Ehrlich choose the
31:57five raw materials. And what happens in the next 10 years is actually their price declined by about
32:0430%. Paul Ehrlich was a huge doofus and scared the living crap out of people. You might wonder,
32:13is Julian Simon a genius or what? No, he's not a genius. It's just basic supply and demand.
32:19If you understand basic supply and demand, you'll understand why prices go down over time. And as
32:25a Russian professor at Columbia once said, just because you have a PhD doesn't mean you can't be
32:33an SOB. Haha. That's very true by the way. And of course, SOB stands for shorts of breath because
32:40he's a good guy. He doesn't curse. Now, did this Paul Ehrlich like lose his job? No, he's still
32:47working at Stanford. Professors and weather forecasters are the only two professions who
32:54can be wrong most of the time and still keep their jobs. My goodness. Now, forget that Paul Ehrlich.
33:01Let's talk about this great Paul Ehrlich, a German Jewish doctor. He coined the term magic bullet,
33:08which means it's a drug or a therapy that will target the bacteria but not harm the human cell.
33:17This is the magic bullet. For example, beta-lactam antibodies, they destroy the beta-lactam. The
33:22bacteria has a beta-lactam, but human beings do not have beta-lactam. This is a magic bullet.
33:29He's the one who coined the term chemotherapy and he named mast cells mast cell, which actually
33:35means food, because he thought that mast cells are related to nutrition. He was naive, but I don't
33:41blame him. He lived in like 1908. That's like a hundred years ago. He's the one who invented
33:48the first actual treatment for syphilis, arsphenamine or salversan, in 1909 and he won
33:57that Nobel Prize. He discovered a staining technique, probably the methylene blue, before
34:03Graham invented or discovered his famous Graham stain. You know, Graham positive and Graham
34:10negative? Yes, indeed. So, if you were a medical student about 100 years ago or 150 years ago,
34:17you didn't have to study microbiology because there was no Graham stain and you didn't have
34:21to study antibiotics because there was no penicillin. Look how the world is changing.
34:28A hundred years is nothing. Some people say that ehrlichiosis, the tick-borne bacteria,
34:35is thanks to Paul Ehrlich. You know, Ehrlich, ehrlichiosis, but I do not know if this is true
34:41or not. What I do know is you treat ehrlichiosis by doxycycline or minocycline. Both of them are
34:48tetracycline. Remember, tetracycline damage your teeth. Paul Ehrlich became very famous and they
34:55named a street after him called Ehrlich Street in Frankfurt, Germany. He died in 1915, but then look
35:04what happened. He was Jewish and in the Third Reich they hated the Jews so much that they even
35:12removed his name from the street, even though he had already passed away. Remember that people
35:20can be evil and the original motto of Google was don't be evil. It's a reminder to all of us
35:29of what can happen when people don't think. Rest in peace, Paul Ehrlich. You were a great man.
35:37Okay folks, here is your homework for today. Homework? Medicosis? Don't be evil. I'm messing
35:43with you. I just love you. So bring a piece of paper and just draw this diagram on it and do
35:49all of this. If you do it like twice or three times, antibiotics for you will become a piece
35:54of cake. Trust me. Please pause the video right now and do it. Please just freaking do it. Which
36:00is the motto of Nike. Just do it. But Medicosis' motto is just freaking do it. And while you're
36:08holding that blank piece of paper, which is now not blank, on the back of this paper, please draw
36:13this for the penicillins and try to figure them out. And if you want to have a strong memory,
36:19use your memory. I see you right now. You're sitting on your butt and watching this video
36:25in the background. Just freaking do it. I love you so much guys. I'm sorry that the video was
36:31long but it's penicillin. Thank you so much. We will continue in the next video.
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